The role of single-nucleotide polymorphism (SNPs) in toxicity of induction chemotherapy based on cisplatin and paclitaxel in patients with advanced head and neck cancer

Oral Oncol. 2019 Nov:98:48-52. doi: 10.1016/j.oraloncology.2019.09.013. Epub 2019 Sep 17.

Abstract

Background: Induction chemotherapy in locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients is potentially associated to serious adverse events. Biomarkers associated with toxicity could tailor its indication. This study evaluated the association between single-nucleotide polymorphisms (SNPs) in metabolic genes and toxicity to induction chemotherapy.

Methods: 59 LAHNSCC phase II clinical trial patients (NCT00959387) were assessed regarding 47 metabolic genes (366 SNPs). Toxicities were graded (CTCAE 3.0) and statistical analysis was performed.

Results: The SNPs rs8187710 (ABCC2) and rs1801131 (MTHFR) were associated to increased risk of gastrointestinal toxicity, whereas the SNPs rs3788007 (ABCG1) and rs4148943 (CHST3) were associated to decreased risk. Two other SNPs, rs2301159 (SLC10A2) and rs2470890 (CYP1A2), were associated with increased risk of hematological toxicity. Nevertheless, these SNPs did not remain significant after adjusting for multiple comparisons.

Conclusions: This study could not demonstrate relationship between SNPs and toxicity to induction chemotherapy in LAHNSCC patients. The small number of patients may have affected the results.

Keywords: Head and neck cancer; Induction chemotherapy; LAHNSCC; Pharmacogenomic; SNP; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use
  • Female
  • Genotype
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Induction Chemotherapy
  • Male
  • Multidrug Resistance-Associated Protein 2
  • Odds Ratio
  • Paclitaxel / adverse effects*
  • Paclitaxel / therapeutic use
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*

Substances

  • ABCC2 protein, human
  • Antineoplastic Agents
  • Multidrug Resistance-Associated Protein 2
  • Paclitaxel
  • Cisplatin